Novel CYP4F22 mutations associated with autosomal recessive congenital ichthyosis (ARCI). Study of the CYP4F22 c.1303C>T founder mutation

Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis (ARCI). However, less than 10% of all ARCI patients carry a mutation in CYP4F22. In order to identify the molecular basis of ARCI among our patients (a cohort of ninety-two Spanish individuals) we performed a mutational analysis using direct Sanger sequencing in combination with a multigene targeted NGS panel. From these, eight ARCI families (three of them with Moroccan origin) were found to carry five different CYP4F22 mutations, of which two were novel. Computational analysis showed that the mutations found were present in highly conserved residues of the protein and may affect its structure and function. Seven of the eight families were carriers of a highly recurrent CYP4F22 variant, c.1303C>T; p.(His435Tyr). A 12Mb haplotype was reconstructed in all c.1303C>T carriers by genotyping ten microsatellite markers flanking the CYP4F22 gene. A prevalent 2.52Mb haplotype was observed among Spanish carrier patients suggesting a recent common ancestor. A smaller core haplotype of 1.2Mb was shared by Spanish and Moroccan families. Different approaches were applied to estimate the time to the most recent common ancestor (TMRCA) of carrier patients with Spanish origin. The age of the mutation was calculated by using DMLE and BDMC2. The algorithms estimated that the c.1303C>T variant arose approximately 2925 to 4925 years ago, while Spanish carrier families derived from a common ancestor who lived in the XIII century. The present study reports five CYP4F22 mutations, two of them novel, increasing the number of CYP4F22 mutations currently listed. Additionally, our results suggest that the recurrent c.1303C>T change has a founder effect in Spanish population and c.1303C>T carrier families originated from a single ancestor with probable African ancestry

Entamoeba histolytica cell movement: A central role for self-generated chemokines and chemorepellents

Entamoeba histolytica cells, the cause of amoebic dysentery, are highly motile, and this motility is an essential feature of the pathogenesis and morbidity of amoebiasis. However, the control of E. histolytica motility within the gut and during invasion is poorly understood. We have used an improved chemotaxis assay to identify the key extracellular signals mediating Entamoeba chemotaxis. The dominant responses we observe are caused by factors generated by E. histolytica cells themselves. Medium that has been conditioned by E. histolytica growth causes both chemokinesis and negative chemotaxis. The speed of random movement is more than doubled in conditioned compared with fresh medium, and cells move efficiently away from conditioned medium by negative chemotaxis. Ethanol, the product of Entamoeba glucose metabolism, is the principal component of the chemokinetic response. The closely related but nonpathogenic Entamoeba dispar shows no change in motility in response to conditioned medium implying that these responses are central to E. histolytica pathogenesis

Experimental field exclosure of birds and bats in agricultural systems ? Methodological insights, potential improvements, and cost-benefit trade-offs

Experimental exclosure of birds and bats constitutes a powerful tool to study the impacts of wildlife on pests and crop yields in agricultural systems. Though widely utilized, exclosure experiments are not standardized across studies. Indeed, key differences surrounding the design, materials, and protocols for implementing field-based exclosure experiments of flying vertebrates increase heterogeneity across studies, and limit our understanding of biodiversity-friendly land use management. We reviewed the available literature on studies in which bird and bat exclosures were applied to study pest control in agricultural settings, and isolated 30 studies from both tropical and temperate land use systems, involving 12 crop types across 14 countries. Focusing on exclosure effects on crop yield, we analyzed effect detectability for a subset of suitable data. We then analyzed the potential of exclosure methods and possible extensions to improve our understanding of complex food webs and ecosystem services affecting the productivity of agricultural systems. While preferences exist in materials (e.g., nylon nets and bamboo frames), experimental exclosure studies of birds and bats differed greatly in their respective design, related costs, and effort ? limiting the generalization and transferability of results at larger spatial scales. Most studies were based on experiments conducted in the United States and the Neotropics, mainly in coffee and cacao farms. A lack of preliminary or long-term data with repeated measurements makes it impossible to apply power analysis in most studies. Common constraints include, among other things, the choice of material and experimental duration, as well as the consideration of local versus landscape factors. We discuss such limitations, related common pitfalls, and options for optimization to inform improved planning, design, and execution of exclosure studies. By doing so, we aim to promote more comparable and transferable approaches in future field research on biodiversity-mediated ecosystem services